Ahmed F. Donia

Living-donor kidney retransplantation: risk factors and outcome

Authors from Mansoura in Egypt present a study of risk factors and outcome from living‐donor renal re‐transplantation. This is sometimes avoided as being unlikely to have a good outcome, but it is shown here to be the treatment of choice in patients who have lost the primary graft.

Levamisole: adjunctive therapy in steroid dependent minimal change nephrotic children

Abstract In children with minimal change nephrotic syndrome (MCNS), the steroid dependent group constitutes an especially difficult case for management. Patients in this group are prone to serious steroid side effects. Additionally, alkylating agents commonly fail to maintain remission and expose patients to more side effects. Therapy with the immunostimulant drug levamisole may therefore be another option in the attempt to maintain remission with minimal side effects. We prospectively treated 20 of our steroid dependent primary MCNS patients with levamisole. All patients were children, with an age range of 3–15 years; 16 were boys and 4 were girls. Remission was firstly induced by steroids, then levamisole was added in a dose of 2.5 mg/kg body weight on alternate days for 6 months. During this period we attempted to withdraw steroids completely and maintain patients on levamisole alone. We followed up our patients for the occurrence of relapse and side effects during this period and for a further 6 months after stopping levamisole. In 11 out of 20 children (55%), we successfully stopped steroids for more than 2 weeks. At the end of the 6-month treatment period (i.e. after 4 months of steroid discontinuation), ten patients (50%) were maintaining remission on levamisole alone. At the end of the 12-month study period (i.e. after 6 months of levamisole discontinuation), five patients (25%) were still in remission without any treatment for the previous 6 months. No significant side effects were reported during levamisole therapy. None of the patients developed neutropenia, but the leukocyte count showed a significant reduction in those who responded to levamisole treatment. We concluded that levamisole therapy for 6 months is a safe and perhaps effective therapy in a subset of children with steroid dependent MCNS to enable an otherwise infeasible withdrawal of steroids. This may be worth a trial before other types of more hazardous adjunctive therapies are considered.

Determination of Cu2 +, Zn2 + and Pb2 + in biological and food samples by FAAS after preconcentration with hydroxyapatite nanorods originated from eggshell

Hydroxyapatite nanorods (HAPNRs) were prepared from recycled eggshell by using precipitation method. The structure of the HAPNRs was physicochemically and morphologically characterized by X-ray diffraction, transmission electron microscopy and Fourier transform infrared spectroscopy. The resulting HAPNRs were used for solid phase extractive preconcentration of Cu(2+), Zn(2+) and Pb(2+) prior to its determination by flame atomic absorption spectrometry. Experimental variables that influence the quantitative extraction of metal ions were optimized by both batch and column methods. The analytes were quantitatively sorbed on the matrix between pHs6 and 9. The maximum sorption capacity of the HAPNRs has been found to be 2.43, 2.37 and 2.53 mmol g(-1) for Cu(2+), Zn(2+) and Pb(2+), respectively, with the preconcentration factor of 250. The 3σ detection limit and 10σ quantification limit for Cu(2+), Zn(2+) and Pb(2+) were found to be 0.72, 0.55 and 5.12 μg L(-1) and 2.40, 1.83 and 17.06 μg L(-1), respectively. The calibration curves were linear up to 250 μg L(-1) for Cu(2+), 300 μg L(-1) for Zn(2+) and 400 μg L(-1) for Pb(2+). Accuracy of the proposed method was verified using certified reference materials (NCS ZC85006 Tomato, Seronorm Trace Elements Whole Blood L-1, Seronorm Trace Elements Whole Blood L-3 and Seronorm Trace Elements Urine). The present method was successfully applied to the analysis of these metal ions in sea water, biological and food samples.

Ketoconazole-Tacrolimus Coadministration in Kidney Transplant Recipients: Two-Year Results of a Prospective Randomized Study

Background/Aims: In developing countries, kidney transplantation is greatly hindered by financial problems, especially due to costly newer immunosuppressive medications. Ketoconazole increases blood levels of tacrolimus and cyclosporine through inhibition of cytochrome P450 microsomal enzymes. We previously reported on the 6-month safety and the outstanding impact on treatment costs of the ketoconazole-tacrolimus combination in kidney transplant recipients. Data of this combination are still lacking in the literature. We hereby report on the 2-year results of our trial. Methods: This prospective, randomized study included 70 live-donor kidney transplant recipients receiving tacrolimus (age 16–45 years, 54 males and 16 females). Patients were randomized into two equal groups: group 1, where ketoconazole 100 mg/day was added, and group 2 (control group). Results: After 2 years, group 1 (ketoconazole) patients still showed a highly significant reduction of the tacrolimus dose (by 53.8%) and cost (by 52.9%) compared with the control group (p < 0.001) and a significant improvement in graft function in comparison to their own initial graft function (p = 0.002). Throughout the 2 years, no side effects of ketoconazole were noted. Conclusion: We conclude that the long-term ketoconazole-tacrolimus combination therapy in kidney transplant recipients during the 2 years is safe, has an outstanding impact on treatment costs and improves graft outcome.

Sirolimus for visceral and cutaneous Kaposi's sarcoma in a renal-transplant recipient

The incidence of Kaposis sarcoma among recipients of solid organs is about 500 times the rate in the general population, suggesting a role for immunosuppression in its development. On the basis of these findings, we investigated the impact of sirolimus on cutaneous and disseminated visceral Kaposis sarcoma in a renal-transplant recipient. The introduction of sirolimus in this patient allowed complete regression of Kaposis sarcoma (cutaneous and visceral) with preservation of excellent renal function. Meanwhile, in view of the available observational reports, we think that sirolimus should be included in the standard treatment for Kaposis sarcoma after transplantation, to permit remission of the sarcoma (both cutaneous and visceral) while preserving the renal function.

Postkidney Transplant Malignancy in Egypt has a Unique Pattern : A Three-Decade Experience

The pattern of posttransplant malignancy varies among transplant units. We report on our single-center experience. Between 1976 and 2007, 1866 kidney transplantations were carried out (1390 males and 476 females, mean age 29.84±10.47 years). Recipients who developed posttransplant malignancy were evaluated (74 patients, 3.97%). Furthermore, their data were compared with those of the malignancy-free recipients (1792 patients). Kaposi sarcoma was the commonest type (36.8%) and had the shortest transplant-to-malignancy period (mean 2.84 years). The lesions were only cutaneous in 75% of cases. Skin cancers were the fourth among posttransplant malignancies (9.2%) and 85.7% of cases were basal cell carcinoma. In our series, age and prior blood transfusion were identified as independent risk factors for the development of posttransplant malignancy. In conclusion, the prevalence and type of posttransplant malignancy vary because of many factors including environmental and genetic factors. In our series, Kaposi sarcoma was the commonest type and, therefore, needs further evaluation.

Effect of Concomitant Administration of Cyclosporine and Ketoconazole in Children with Focal Segmental Glomerulosclerosis

Background: Focal segmental glomerulonephritis (FSGS) is now the most common primary glomerulonephritis that leads to end-stage renal disease in both adults and children. Cyclosporine (CsA) is a well-known and effective immunosuppressive agent that has become a cornerstone of immunotherapy in solid organ transplantation and it has been used in the treatment of FSGS for over 15 years. The deliberate use of ketoconazole (keto) to reduce the need for CsA is not new, but it is particularly relevant because of the high cost of CsA. Many studies have documented this benefit in renal and cardiac transplants, but this co-administration has not been reported in children with nephrotic syndrome (NS). Methods: This study included 116 children (below 18 years of age) with primary FSGS who were steroid resistant or dependent and received CsA therapy. Among them, 88 received daily keto therapy (keto group) in a dose of 50 mg with concomitant decrease of CsA dose by one third, while 28 patients received CsA alone (non-keto group). Mean (±SD) age was 6.17 ± 4.68 years and male to female ratio was 1.9:1. The great majority of the study population received the drugs for 1–2 years. The characteristics of both groups were comparable. Results: Co-administration of keto significantly reduced mean doses of CsA by 46% at 1 year with overall net cost savings of 36%. It also significantly improved the response to CsA therapy and decreased the frequency of renal impairment. No significant side effects for keto were observed. Conclusion: Co-administration of keto and CsA in idiopathic FSGS children is safe. This combination not only reduces the costs but also may improve the response to CsA and stabilize the renal function.

Impact of Donor Source on the Outcome of Live Donor Kidney Transplantation: A Single Center Experience

Background Renal transplantation is the ideal method for management of end-stage renal disease. The use of living donors for renal transplantation was critical for early development in the field and preceded the use of cadaveric donors. Most donors are related genetically to the recipients, like a parent, a child, or a sibling of the recipient, but there are an increasing percentage of cases where donors are genetically unrelated like spouses, friends, or altruistic individuals. Donor shortages constitute the major barrier for kidney transplantation, and much effort has been made to increase the supply of living donors. The impact of donor source on the outcome of renal transplantation is not adequately studied in our country. Objectives The aim of the study was to evaluate the impact of donor source on the outcome of live donor kidney transplantation. Patients and Methods From March 1976 to December 2013, the number of patients that underwent living renal transplantation sharing at least one HLA haplotype with their donors was 2,485. We divided these patients into two groups: (1) 2,075 kidney transplant recipients (1,554 or 74.9% male and 521 or 25.1% female) for whom the donors were living related, (2) 410 kidney transplant recipients (297 or 72.4% male and 113 or 27.6% female) for whom the donors were living unrelated. All patients received immunosuppressive therapy, consisting of a calcineurin inhibitor, mycophenolate mofetil, or azathioprine and prednisolone. We compared acute rejection and complication rates, as well as long-term graft and patient survival of both groups. Demographic characteristics were compared using the chi-square test. Graft survival and patient survival were calculated using the Kaplan-Meier method. Results The percentages of patients with acute vascular rejection were significantly higher in the unrelated group, while percentages of patients with no rejection were significantly higher in the related group, but there were no significant differences regarding patient and graft survivals between both groups. Conclusions Kidney transplant recipients who received their grafts either from live related donors or live unrelated donors had comparable patient and graft survival outcomes.

Adolescent with Hypothyroidism Induced Rhabdomyolysis and AcuteKidney Injury

Objectives: Rhabdomyolysis is a potentially life-threatening syndrome. Hypothyroid patients may present with myopathy and mild elevation of CK levels; however, overt rhabdomyolysis is extremely rare, and few cases have been described. Hypothyroidism should be considered in patients presenting with renal impairment associated with rhabdomyolysis. Case report: A 24-year-old young man with accidently discovered hypothyrodism on admission presented with generalized myalgia, profound proximal muscle weakness of the bilateral lower extremities, anuria, vomiting and dark colored urine lasting for three days. Neurological examination revealed bilateral marked weakness and tenderness of muscles of both lower and upper extremities. Urine had dark red appearance and urinalysis showed blood reaction with dipstick test, but there were no erythrocytes on microscopic examination. Serum creatine phosphokinase and myoglobin levels were elevated. Thyroid stimulating hormone (TSH) levels were high, and Free Thyroxine (T4) and Triiodothyronine (T3) levels were low, renal function tests showed acute kidney injury. Other causes of rhabdomyolysis such as muscular trauma, drugs, toxins, infections, vigorous exercise, and electrolyte abnormalities were excluded. Hemodialysis was administered for five sessions. After L-thyroxine therapy, thyroid function tests normalized, muscle strength improved, serum muscle enzyme levels returned to normal levels, and renal function tests recovered. Conclusion: Hypothyroidism should be considered in patients presenting with renal impairment associated with rhabdomyolysis.

Co-Administration of Cyclosporine and Ketoconazole in Children with Minimal Change Nephrotic Syndrome

Background/Aims: The use of cyclosporine A (CsA) in the treatment of idiopathic nephrotic syndrome was firstly reported in 1986. On the other hand, many studies have documented the benefit of ketoconazole (keto) administration in renal and cardiac transplant adults treated with CsA, but this co-administration has not been reported in children with minimal change disease (MCD). Thus, deliberate use of keto to reduce the need for cyclosporine is not new, but it is particularly relevant because of the high cost of cyclosporine. Methods: This study included 46 children with MCD who were steroid resistant or dependent and received CsA. Among them, 31 received daily keto therapy (keto group) in a dose of 50 mg with concomitant decrease of the CsA dose by one third while 15 patients received CsA alone (non-keto group). Results: The mean (±SD) duration of CsA treatment was 25.7 ± 13.7 months. The characteristics of both groups were comparable. Co-administration of keto significantly improved the response to CsA therapy (from 60 to 94%) and decreased the frequency of renal impairment (from 27 to 3%). Hepatic function remained within the normal range in both groups. Co-administration of keto significantly reduced mean doses of CsA with overall net cost savings of about 34%. Conclusion: From this study, we may conclude that co-administration of low dose ketoconazole to cyclosporine in children with idiopathic MCD is safe. This combination significantly reduces CsA cost and, moreover, keto may improve the response to cyclosporine and may have a favorable effect on the kidney function.